Rifampin Drug-Drug-Interaction Studies: Reflections on the Nitrosamine Impurities Issue

Clin Pharmacol Ther. 2023 Apr;113(4):816-821. doi: 10.1002/cpt.2652. Epub 2022 Jun 22.

Abstract

Clinical development of new drugs may require dedicated drug-drug interaction (DDI) studies, such as to evaluate the effect of cytochrome P450 3A induction on the pharmacokinetics of investigational drugs. However, as a result of N-nitrosamine impurity findings in marketed rifampin formulations, the application of rifampin in DDI studies has been halted. This mini-review considers the root cause and impact of the nitrosamine impurity as well as alternative options for the continued conduct of DDIs.

Publication types

  • Review

MeSH terms

  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP3A Inducers* / pharmacokinetics
  • Drug Interactions
  • Drugs, Investigational
  • Humans
  • Rifampin* / pharmacokinetics

Substances

  • Rifampin
  • Cytochrome P-450 CYP3A Inducers
  • Cytochrome P-450 CYP3A
  • Drugs, Investigational